title: Beyond calcineurin inhibitors: emerging agents in kidney transplantation.
abstract: OBJECTIVE
  Despite their effectiveness, calcineurin inhibitors (CNIs) represent a major obstacle in the improvement of long-term graft survival in transplantation. The identification of new agents to implement CNI-free regimens is the focus of current transplant research. The purpose of this review is to summarize the novel immunosuppressive agents, including details about their mechanisms of action, stages of development, potential benefits and challenges.
  
  
  RESULTS
  Targeting costimulation with belatacept is now an option for controlling the alloimmune response and has proved to be more effective in preserving long-term allograft function than CNIs despite an increased rate of acute rejection in some studies. mTOR inhibitors are also promising with their remarkable antineoplastic properties, though frequent side-effects may limit their broader use. Other agents under development include JAK inhibitors, CD40 blockade and leukocyte adhesion blockers, with unique potential benefits and side-effects in transplantation.
  
  
  CONCLUSIONS
  Novel immunosuppressive agents are now available for use in CNI-free regimens in solid organ transplantation. Timing of initiation as well as long-term efficacy and safety are questions that remain to be answered in future clinical trials.
authors.affiliation: Transplantation Research Center, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Kassem
authors.initials: K
authors.lastname: Safa
authors.forename: Leonardo V
authors.initials: LV
authors.lastname: Riella
authors.forename: Anil
authors.initials: A
authors.lastname: Chandraker
mesh_terms: D000069594:Abatacept; D019013:CD40 Antigens / Q000037:antagonists & inhibitors; D018968:CD58 Antigens / Q000187:drug effects; D065095:Calcineurin Inhibitors; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D053612:Janus Kinases / Q000037:antagonists & inhibitors; D016030:Kidney Transplantation / Q000379:methods* / Q000639:trends; D008213:Lymphocyte Activation / Q000187:drug effects; D016169:Lymphocyte Function-Associated Antigen-1 / Q000187:drug effects; D018448:Models, Immunological; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D019013:CD40 Antigens; D018968:CD58 Antigens; D065095:Calcineurin Inhibitors; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D016169:Lymphocyte Function-Associated Antigen-1; D000069594:Abatacept; C546842:MTOR protein, human; D053612:Janus Kinases; D058570:TOR Serine-Threonine Kinases; D011493:Protein Kinase C